A DNA Methylation Test for Follow-up of Patients with Non-Muscle Invasive Bladder Cancer - Expert Commentary

DNA methylation is known to be altered in many cancers, including bladder cancer, and has therefore been a promising alternative for surveillance in patients with non-muscle invasive bladder cancer (NMIBC). The Bladder EpiCheck test has been validated for detecting bladder cancer by evaluating 15 genomic biomarkers to yield a score from 0 to 100.

Previous studies have shown adequate results in terms of sensitivity and specificity of the test, particularly in high-risk cancers. Ragonese et al. aimed to test the performance of the EpiCheck test in a heterogeneous cohort of NMIBC patients.

The study cohort consisted of 231 patients who had a history of NMIBC. During the study period, 71 patients developed bladder cancer recurrence. 78 patients had a positive EpiCheck result with a score greater than or equal to 60. Interestingly, 57 patients who had a positive test experienced NMIBC recurrence. Patients also underwent cytology tests, with 73 patients having a positive test and 49 having NMIBC recurrence. Overall sensitivity was 69% for cytology and 80% for EpiCheck, while specificity was 82% for cytology and 84% for EpiCheck. The negative predictive value was 83% for cytology and 89% for EpiCheck, while the positive predictive value was 67% for cytology and 73% for EpiCheck. Upon stratification of patients by grade, the sensitivity in high-grade NMIBC patients was 91% for EpiCheck and 81% for cytology, while specificity was 85% for EpiCheck and 83% for cytology. The negative predictive value was 96% for EpiCheck and 92% for cytology. In a subset of patients receiving intravesical bacillus Calmette-Guérin (BCG) treatment, sensitivity was 88% for EpiCheck and 73% for cytology, while specificity was 97% for EpiCheck and 85% for cytology. The negative predictive value was 92 % for EpiCheck and 82% for cytology. Finally, in a subset of patients with carcinoma in situ, sensitivity was 87.5% for EpiCheck and 78% for cytology, while specificity was 88.1% for EpiCheck and 74% for cytology. The negative predictive value for this subcategory was 97.5% for Epicheck and 94.3% for cytology.

The present study by Ragonese et al. shows robust performance for EpiCheck in detecting NMIBC that parallels that of the more traditional cytology technique. The EpiCheck test also poses some unique advantages, such as a higher potential for detecting carcinoma in situ that may be missed in cystoscopy evaluations. In addition, EpiCheck could even outperform cystoscopy to detect select high-risk NMIBC cases. Intravesical treatments are known to affect urothelial cell structure. They could therefore lead to false positive results in cytology tests, but not with EpiCheck. Using EpiCheck for follow-up of NMIBC patients could reduce the number of cystoscopies and extend the interval between tests. However, studies with longer follow-up periods are needed to track whether patients with negative EpiCheck tests develop late recurrences.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. Ragonese M, Gianfrancesco LD, Palermo G, et al. The Role of Bladder Epicheck Test In Follow-Up of Patients with Non-Muscle Invasive Bladder Cancer. Clin Genitourin Cancer. 2022;20(4):e271-e275. doi:10.1016/j.clgc.2022.03.009
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